Estradiol (E2) is involved in the control of food intake in female rats, e.g., E2 alone abolishes the increased food intake that occurs in ovariectomized (OVX) rats; and in ovarian-intact, cycling rats, the proestrous rise in E2 secretion leads to decreased food intake during estrus. E2 also appears to regulate energy expenditure (EE). This has been suggested by studies demonstrating that pair-feeding of OVX rats to the amount of food they consumed daily prior to OVX does not prevent obesity. I have novel and exciting preliminary data suggesting that this effect may be mediated by distinct changes in locomotor activity (LA). Specifically, OVX mice do not exhibit increased food intake, yet they become obese, supporting the notion that E2 regulates EE. My preliminary data shows that LA is drastically decreased by OVX in mice, suggesting that E2-regulation of LA and EE may be more prominent in mice. There is some evidence that E2 regulates resting EE, but the potential mechanisms remain unknown. The purpose of this proposal is to uncover the neural mechanisms underlying the capacity of E2 to modulate EE and to delineate the impact of E2-mediated behavioral and physiological actions that are protective against the development of obesity. [unreadable] [unreadable] [unreadable]